NanoBio Influenza Mucosal Vaccine Program:
The U.S. Food and Drug Administration (FDA) approved NanoBio's Investigational New Drug (IND) application for the Phase 1 clinical study of NB-1008, a seasonal influenza vaccine administered via a nasal dropper during Q1, 2009. The resulting randomized, controlled study in the United States involved 199 healthy human volunteers and was initiated in April of 2009. The primary endpoints were safety and immunogenicity as determined by neutralizing serum antibodies. In this recently completed study all doses were well tolerated and significant immune responses were observed.
NanoBio has demonstrated protection and prophylaxis against influenza with prototype intranasal (IN), subcutaneous (SC) and intramuscular (IM) vaccines in several studies partially represented below:
- Significant immune response with antigen sparing properties demonstrated in multiple studies in ferrets: A single administration of NanoBio's nasally-delivered influenza vaccine containing half the standard antigen dose elicited immune responses in ferrets that were more than 20 times higher than that generated by two injections of the currently-approved vaccines. Following nasal immunization the ferrets, which represent the most relevant influenza animal model for humans, were then challenged with live influenza virus and all were protected. These data were released at ICAAC/IDSA 2008 as a scientific presentation.
Three follow-on studies in a total of 354 ferrets, demonstrated very robust HAI titers in naive ferrets after only one internasal vaccination using significantly less antigen than utilized in the study described above. This study report and other preclinical data were released at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September, 2009 and are available on the "Conferences" page of this web site.
- Strong immune responses demonstrated in subcutaneous (SC) and intramuscular (IM) models: Studies in mice in which immune responses were evaluated following administration of 5µg doses of recombinant H5N1 pandemic flu antigen combined with the company’s novel nanoemulsion vaccine adjuvant. These studies are unique because the adjuvant was administered for the first time by subcutaneous (SC) and intramuscular (IM) injections. The mice that received either SC or IM H5 antigen combined with nanoemulsion had maximal immune responses at least a 1000 fold higher than control animals that received the same antigen IM without the nanoemulsion adjuvant. SC and IM administered NanoBio adjuvanted vaccines should share many of the advantages, including antigen-sparing properties, previously demonstrated in studies where the adjuvant was administered intranasally.
- Protection after mucosal vaccination in mice: 100% survival has been demonstrated in several studies in which mice were exposed to highly lethal doses of several different influenza strains.
- Cross strain immunogenicity after vaccination against a single strain: Mice were vaccinated with the H2N2 strain, then challenged with a lethal dose of H2N2. 100% of these mice survived. These same mice were then rechallenged with a lethal dose of a different strain, H1N1, again resulting in a 100% survival. Cross strain immunogenicity was also demonstrated in several studies in Ferrets in 2009.
- Prophylaxis after application of an antigen free nanoemulsion to the nares: An antigen free nanoemulsion was applied to the nares of mice, a lethal dose 80 influenza was then nebulized into chamber, eighty percent of animals pretreated with saline alone died from influenza pneumonia. Seventy percent of the antigen free emulsion-treated animals survived the challenge.
Many of the safety studies, the stability data and the manufacturing scale-up activities included in the influenza program are integral to the development programs of other nasally delivered vaccines
within NanoBio's universal nanoemulsion adjuvant & antigen delivery system.
The currently circulating influenza viruses that cause human disease are defined by two different surface protein components know as antigens. These antigens are spike-like structures called haemagglutinin (H) and neuraminidase (N). The identity of influenza viruses is defined by these antigens. Examples include: H1N1 and H5N1.
The virus is highly infectious and passed from person to person through the air by droplets and small particles excreted when infected individuals cough or sneeze. The influenza virus enters the body through the nose or throat. It then takes between one and four days for the person to develop symptoms. Individuals suffering from influenza can be infectious from the day before they develop symptoms until seven days afterwards.
The influenza A viruses have undergone three major genetic changes, mainly in their H-component during the past century, resulting in global pandemics and large tolls in terms of both disease and deaths. Most recently, limited outbreaks of a new influenza subtype A (H5N1) directly transmitted from birds to humans ("Bird Flu") have occurred in several regions of the world.